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Chronic reflux esophagitis precedes Barrett's esophagus, which is defined as the columnar-lined epithelium replacing the original squamous epithelial cell lining of the esophagus. Barrett's esophagus carries a risk of malignant transformation to adenocarcinoma. Patients with complicated Barrett's esophagus reflux significantly greater amounts of both acid and duodenal contents than patients with uncomplicated Barrett's esophagus (Vaezi and Richter, 1995). Individuals with a history of gastrectomy often suffer from alkaline reflux esophagitis, and their esophageal carcinoma often develops in the lower third of the esophagus, whereas esophageal carcinoma in patients not subjected to gastrectomy is most frequently located at the middle third of the esophagus (Maeta et al., 1990). Gastric-stump carcinogenesis is associated with duodenogastric reflux. Development of experimental esophageal carcinoma induced by carcinogens is promoted by reflux of duodenal contents (Pera et ab, 1989; Seto et al., 1991; Attwood et al., 1992; Clark et al., 1994) and duodenal contents per se induce rat gastric carcinoma (Miwa ei ai., 199%). This clinical and experimental evidence favors the view that esophageal mucosa may be susceptible to duodenal contents in esophageal carcinogenesis. We have reported that duodenogastric reflux is associated with forestomach and esophageal carcinogenesis in rats (Miwa et al., 1994). However, it is still unresolved which secretions of the refluxate, duodenal or gastric contents, are responsible. In this study we investigate whether reflux of duodenal andtor gastricjuice can cause esophageal carcinogenesis in rats. MATERIAL AND METHODS Experimental animalsWistar male rats weighing approximately 250g were used. They were housed 3 to a cage, and maintained under conditions of 22 2 3°C room temperature and 55 _C 5% humidity with a 12-hr light-dark cycle. They were fed a standard solid chow CRF-1 (Charles River, Japan) and tap water. Surgical proceduresAfter 24 hr fasting, the rats received an upper abdominal incision under diethyl-ether inhalation anesthesia. Then one of the surgical procedures illustrated in Figure 1 was performed on each rat.Gastro-duodeno-esophageal reflux (GDER) (n = 30). After the bilateral vagus nerves were preserved, the abdominal esophagus was transected under the diaphragm, and the distal cut end was closed with sutures. The esophageal stump was anastomosed end-to-side to a loop of jejunum 4 cm distal to Treitz's ligament in an ante-colic manner. This procedure allowed gastro-duodenal contents to flow back into the esophagus.Duodeiio-esophageal reflux (DER) (n = 30). The glandular stomach and forestomach were removed (total gastrectomy), before the duodenal stump was closed with sutures. The esophageal stump was then anastomosed end-to-side to the jejunum approximately 4 cm distal to Treitz's ligament. This surgery induced reflux of duodenal contents into the esophagus.Gastro-esophageal reflu (GER) (n = 30). After the bilateral vagus nerves were preserved, the abdominal esophagus w...

Background. To determine the extent of dissection in curative resection for cancer of the pancreatic head, the mode of recurrence was determined at autopsy and by radiographic examinations. Materials and Methods. Records of 45 patients who had undergone macroscopically curative resection of carcinoma of the head of pancreas were analyzed to determined the mode of recurrence. The mode of recurrence was divided into four types: hepatic metastasis, peritoneal dissemination, retroperitoneal recurrence, and distant metastasis. Retroperitoneal recurrence was subdivided into lymph node metastasis and local recurrence, primarily neural invasion and lymphatic invasion. Results. Thirty patients experienced disease recurrence. Patients with Stage I or II disease experienced recurrence significantly less often than did patients with Stage III or IV disease (P < 0.05). Local retroperitoneal recurrence was discovered in 12 of 15 (80%) postmortem examinations, hepatic metastasis in 10 (66%), peritoneal dissemination in 8 (53%), and lymph node recurrence in 7 (47%). In 15 antemortem studies, retroperitoneal recurrence occurred most frequently (87%), followed by hepatic metastasis (53%). Almost all patients with liver metastasis also had local retroperitoneal recurrence. Conclusions. The frequency of retroperitoneal recurrence of carcinoma of the head of the pancreas suggests that retroperitoneal resection, including nerve plexi and lymph nodes, should be included in curative resections for patients with Stage I or II pancreatic cancer.

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We performed continuous hyperthermic peritoneal perfusion (CHPP) or continuous normothermic peritoneal perfusion (CNPP) combined with cisplatin (CDDP) 300 mg/kg and mitomycin C (MMC) 30 mg/kg in an attempt to prevent peritoneal recurrence after surgery for gastric cancer. Twenty-two patients were treated with perfusion using about 10 liters of saline heated to 41 degrees to 42 degrees C (CNPP group); 18 patients were treated with saline heated to 37 degrees to 38 degrees C (CNPP group); and 18 patients underwent only gastric surgery without perfusion (control group) in a randomized control study. There were two deaths (9%) due to peritoneal recurrence in the CHPP group, four (22%) in the CNPP group, and four (22%) in the control group. The 1-, 2-, and 3-year survival rates were 95%, 89%, and 68%, in the CHPP group; 81%, 75%, and 51%, in the CNPP group; and 43%, 23%, and 23%, in the control group, respectively. There was a significant difference between the three survival curves by the log-rank test (p < 0.01). This difference showed that CNPP and CHPP are both effective procedures for preventing peritoneal recurrence. The maximum concentrations in the perfusate of total and free CDDP with 300 mg administration were 12.2 and 10.1 micrograms/ml, respectively, at the end of the perfusion, and the maximum concentrations of total and free CDDP in plasma were 2.1 and 1.0 micrograms/ml, respectively. The maximum concentrations of MMC in perfusate and plasma with 30 mg administration were 1.00 and 0.05 micrograms/ml, respectively, which are intraperitoneally cytotoxic but systemically safe concentrations.

Fifty-five patients with high-grade advanced gastric cancer in whom the presence of stage IV was confirmed by preoperative diagnostic imaging were treated with PMUE therapy by a combined use of cisplatin (CDDP) 75 mg/m2, mitomycin C (MMC) 10 mg/body, etoposide 150 mg/body, and UFT (a combination of 1-(2-tetrahydrofuryl)-5-fluorouracil and uracil in a molar ratio of 1:4) 400 mg/day. CDDP and MMC was administered intravenously on the first day, followed by etoposide 50 mg/day on the 3rd, 4th, and 5th days. All the patients had measurable lesions that were evaluated by computed tomography scanning before and after the treatments. These patients were allocated randomly to two groups. Of these cases, 29 belonged to the neoadjuvant chemotherapy (NAC) group to whom PMUE therapy was given preoperatively; the remaining 26 patients underwent operation first and received PMUE thereafter (control group). Background factors did not differ significantly between the two groups. The response rate was higher in the NAC group than in the control group (62% in the former versus 35% in the latter). The resectability rates were 79% and 88% in the NAC and control groups, respectively. However, the rate of potentially curable cases was higher in the NAC group than in the control group (38% in the former versus 15% in the latter). Among the nonresection cases, the prognosis was highly unfavorable in both groups. In the resection cases, however, the survival rate was significantly better in the NAC group than in the control group. These results may indicate that in patients with high-grade, advanced gastric cancer initial chemotherapy (neoadjuvant chemotherapy) and then surgery should be considered.

We examined amplification of the c-met, c-erbB-2, and epidermal growth factor receptor (EGFR) gene in the patients with primary gastric cancer, and compared the data with clinical features in order to clarify the relationship between oncogenic abnormality and clinical features. Oncogene amplifications were examined by slot blot hybridization using DNAs extracted from formalin-fixed and paraffin-embedded tissues of primary gastric cancers. Seven of the seventy cancers (10.0%) had c-met gene amplification, nine (12.9%) had c-erbB-2 gene amplification, and six (8.6%) had EGFR gene amplification, respectively. Eighteen cases (25.7%) exhibited one or multiple oncogene amplification, and two cases (2.9%) exhibited simultaneous amplification of the three genes. The cases with c-met gene amplification tend to show invasive character and were related to peritoneal dissemination. The cases with c-erbB-2 gene amplification were related to lymph node metastasis. The cases with EGFR gene amplification had large tumors and were in highly advanced stage. The survival rate in patients with oncogene amplification was significantly lower than that in patients without amplification. Our data indicated that these genes were related to growth and metastasis of gastric cancer. Furthermore, this study about the three genes suggested that the type of activated gene might decide on the type of metastasis and clinical features.